Antigen/MHC-specific T cells are preferentially exported from the thymus in the presence of their MHC ligand

Transgenic mice expressing a T cell receptor heterodimer specific for a fragment of pigeon cytochrome c plus an MHC class II molecule (I-E k) have been made. We find that H-2 k αβ transgenic mice have an overall increase in the number of T cells and express a 10-fold higher fraction of cytochrome c-reactive cells than H-2 b mice. Surface staining of thymocytes indicates that in H-2 b mice, T cell development is arrested at an intermediate stage of differentiation (CD4 +8 +, CD3 lo). Analyses of mice carrying these T cell receptor genes and MHC class II I-E α constructs indicate that this developmental block can be reversed in H-2 b mice by I-E expression on cortical epithelial cells of the thymus. These data suggest that a direct T cell receptor-MHC interaction occurs in the thymus in the absence of nominal antigen and results in the enhanced export of T cells, consistent with the concept of “positive selection.”